This is the first competing renewal application for the Environmental Health Sciences (EHS) Core Center at the University of Michigan, submitted in the final year of the initial four years of NIEHS support. The Center is organized around the theme of critical windows of susceptibility to environmental exposures as important determinants of disease, forming the Michigan Center of Lifestage Environmental Exposures and Disease (M- LEEaD). Lifestage, as used in this application, refers to clinically-recognized stages of development, mid-life, and aging that pertain to the preconception, prenatal, infant, child, adolescent, reproductive age adult, and aging adult periods of life. The Center builds on a strong foundation of research activity and support at the University of Michigan in this emergent arena of environmental public health, with 16 NIEHS grants moving into the next funding period that includes a Children's Environmental Health and Disease Prevention Research Center and participation in a Superfund Research Program Center. The mission of M-LEEaD is to accelerate research that defines impacts of environmental exposures during vulnerable stages of life, and to promote translation of these findings to improve medical and public health interventions for the mitigation of chronic disease. The Center implements its mission through infrastructural support of established and new investigators applying novel transdisciplinary approaches that increase understanding of mechanisms by which environmental exposures target vulnerable stages of life. Support for research is provided through integrated Center programs that include a Pilot Project Program, three Facility Cores, and three Research Teams to create synergy for stimulation of innovative research. The Facility Cores are: 1) Integrated Health Sciences Core (IHSC); 2) Exposure Assessment Core (EAC); and 3) Omics and Bioinformatics Core (OBIC). Research Teams are organized around key mechanistic pathways of disease: 1) Inflammation & Oxidative Stress; 2) Genomics & Epigenomics; and, 3) Endocrine & Metabolic Disruption. Research is coupled with the engagement of stakeholder communities through the Community Outreach and Engagement Core (COEC) and training of future leaders in EHS through the Center Career Development Program. The functioning of the Center is overseen by an Administrative Core. M-LEEaD strives to accomplish its mission through the following specific aims: 1) Integrate and build upon existing institutional programs and facilities to provide structure and resources that accelerate understanding of the complex relationships among environmental exposures, human biology, and disease; 2) Foster integration, coordination, and cooperation among investigators across traditional disciplinary boundaries to conduct high-quality research that translates to improved strategies towards preventing environmentally-induced disorders; 3) Build programmatic and scientific capacity through support for scientists at critical career stages, but especially those at early- and mid-career stages, to engage in research that addresses critical, emerging questions in environmental health; and, 4) Interact with affected communities in a bidirectional manner to identify community environmental health concerns and to translate research findings into community engagement opportunities.